Adaptive Deep Brain Stim Shows Promise in Parkinson's

Approach can induce stable control of PD-related motor disturbances

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Adaptive deep brain stimulation (aDBS) seemed to effectively controlled motor symptoms, and was safe and well tolerated, in patients with advanced Parkinson's disease.

Daily life activities did not offset the improvement that aDBS provided, and the combination of levodopa and aDBS did not result in dyskinesia.

Adaptive deep brain stimulation (aDBS) seemed to effectively control motor symptoms, and was safe and well tolerated, in patients with advanced Parkinson's disease, according to international researchers.

In the 8-hour experiment, aDBS and oral levodopa improved the motor "off" scores at the end of the levodopa dose by 30%, reported Alberto Priori, MD, PhD, of the University of Milan, and colleagues.

Daily life activities did not offset the improvement that aDBS provided, and the combination of levodopa and aDBS did not result in dyskinesia, they wrote online in Neurology.

"To the best of our knowledge, this is the longest experiment with aDBS," the authors stated. "Our observations showed that changing DBS voltage linearly with beta rhythm provides constant benefit for hours of unrestricted patient activity and in conjunction with normal levodopa assumption."

Continuous DBS is an established treatment for essential tremor and Parkinson's disease. Adaptive DBS is being studied as a way to actively respond to a patient's brainwaves, delivering stimulation when needed. Beta band oscillation is modulated by movement planning and execution, levodopa, and DBS, and is considered a promising biomarker for aDBS.

As a preliminary step toward developing an implantable aDBS device, the researchers aimed to investigate whether aDBS could follow and control fluctuations using beta band changes, and whether it was tolerated and safe for 8 hours.

The open-label, nonblinded study of 11 patients looked at motor fluctuations during spontaneous, unrestricted daily life activities. It enrolled rigid-akinetic patients with advanced Parkinson's who had surgery for subthalamic nucleus DBS electrode implantation from March 2016 to January 2017.

The experimental sessions took place after DBS surgery, before the DBS leads were connected to the subcutaneous pulse generator. Patients were implanted bilaterally, but studied unilaterally.

The experiment was conducted over 2 days; each day had one 8-hour session. After 12 hours of medication withdrawal, each session started with a baseline assessment (medication "off," stimulation "off").

On day 1, patients took their first morning medication and were assessed when their medication was effective (medication "on," peak dose at about 45-60 minutes after taking medication) and when the medication effects ended (medication "off," end dose 60-90 minutes after the peak dose). The same procedure was repeated for 8 hours.

On day 2, a portable aDBS prototype was switched "on" immediately after the baseline assessment. Clinical assessments on day 2 followed the same program as day 1.

The researchers monitored patient activity during these sessions through clinical diaries, which patients completed every 30 minutes, and a bracelet accelerometer. They also collected beta band data and, on day 2, stimulation amplitude.

They found that aDBS reduced Unified Parkinson's Disease Rating Scale part III (UPDRS III) motor scores by almost 30% when patients were "off" medication on day 2 compared to day 1. Levodopa and aDBS did not result in dyskinesia.

As expected, beta amplitudes responded to levodopa, as did activities like talking, walking, and relaxing. The beta band reactivity induced by daily life activities did not offset the improvement aDBS made. Patients reported no adverse effects related to aDBS or complaints.

While this experiment shows aDBS has promise to tackle unmet needs, future studies need validate how long-term treatment will work, observed Daniel Weiss, MD, of the University of Tubingen in Germany, and Joao Massano, MD, of the University of Porto in Portugal.

"Before aDBS can translate to regular clinical therapy in the future, important steps still have to be taken," they wrote in an accompanying editorial. "Customized software and hardware solutions that allow stable, long-term recordings and ongoing adaptive therapy delivery for months and years are under development."

"Moreover, although beta band amplitude modulations correlate with rigidity and bradykinesia, other PD motor symptoms such as tremor, dyskinesia, and freezing phenomena do not and will probably require alternative solutions owing to the differences in their electrophysiologic surrogates," they stated.

The study had limitations: Because aDBS used an external prototype immediately after surgery for DBS electrode placement, edema limited the ability to mimic a more stable chronic phase. The aDBS was unilateral, and the study was open-label and unblinded. Also, the daily life activity analysis was based on self-reported diaries and data from a single accelerometer, which could not track different activities that occurred at the same time.